Disease relevance of Cdx2

• Cdx2 staining tendency was decreased in colon tumors and adenocarcinomas compared to normal mucosa and ACF, which stained in 100% of cases [1].
• Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma [2].
• This report describes a study using the rat insulinoma cell line RIN-1056A, which abundantly expresses both insulin and proglucagon (glu), and relatively high amounts of endogenous Cdx-2 [3].

High impact information on Cdx2

• The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation [4].
• These conclusions are consistent with the role of Cdx2 in regulating intestinal cell differentiation [4].
• As homeodomain proteins play major roles in directing the regionalization of body parts and in organogenesis and cellular phenotypic specification, a reduction of Cdx-2 expression in the late stages of colorectal carcinogenesis may reflect a concomitant deviation of the neoplastic tissue from the normal intestinal epithelial phenotype [2].
• The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine [5].
• The gene expression patterns for Cdx2-inducing cells and control cells were examined using oligonucleotide arrays [6].

Biological context of Cdx2

• These data indicate that HB-EGF gene expression can be regulated by Cdx2 and serves to mediate the control of Cdx2 of the proliferation and migration of IEC-6 cells [7].
• Reporter gene analyses showed that the HB-EGF gene promoter is Cdx2 responsive and that the activity of the promoter in the IEC-6 cells depends on the number of consensus Cdx2-binding site-like sequences [7].
• The caudal-related homeobox transcription factor (Cdx2) plays an important role in intestinal development, differentiation, and homeostasis [6].
• Furthermore, expression of Cdx2 in IEC-6 cells conferred the ability to express a Math1 reporter gene containing a Math1 enhancer [8].
• Forced expression of the Cdx2 gene in undifferentiated intestinal crypt cells induces the development of a differentiated phenotype [9].

Anatomical context of Cdx2

• Using cDNA microarrays, we identified heparin-binding EGF-like growth factor (HB-EGF) as one of the genes induced by intestinal-specific transcription factor Cdx2 in an intestinal undifferentiated rat cell line, intestinal epithelial cell (IEC)-6 [7].
• Heparin-binding EGF-like growth factor gene transcription regulated by Cdx2 in the intestinal epithelium [7].
• We engineered a rat intestinal epithelial cell line, IEC-6, with minimal endogenous Cdx2 expression to express exogenous Cdx2 [6].
• Furthermore, Math1-producing epithelial cells that showed positive immunostaining for Cdx2 were also observed in intestinal metaplastic mucosa from human and Cdx2 transgenic mouse stomachs, although they were not detected in normal gastric mucosa of humans and mice [8].
• The complex is recognized by Cdx2 antibody and is more abundant in differentiated enterocytes [4].

Associations of Cdx2 with chemical compounds

• The skeletal alterations seen in vitamin A deficiency are associated with posterior shifts in the mesodermal expression of Hoxa-4, Hoxb-3, Hoxd-3, Hoxd-4, and Hoxa-9 mRNAs, whereas the anterior domains of Hoxb-4 and Cdx2 expression are unaltered [10].
• Cdx1 and Cdx2, known to be transcriptional factors related to intestinal proliferation and differentiation, were more highly expressed in STZ, OLETF and GK rats than in the respective controls [11].
• Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element [12].

Other interactions of Cdx2

• HB-EGF may function as one of the mediators of Cdx2 and may be associated with the proliferation and migration in the intestinal epithelium [7].

Analytical, diagnostic and therapeutic context of Cdx2

• Identifying target genes regulated downstream of Cdx2 by microarray analysis [6].
• METHODS: Nuclear protein bound to the lactase gene cis element, CE-LPH1, was analyzed by electrophoretic mobility shift assays and supershifts with Cdx2 antibody [4].
• By immunohistochemistry with a polyclonal Cdx-2 antibody we have shown that Cdx-2 expression is markedly reduced in the later stages of human colorectal carcinogenesis, namely, high grade dysplasia and invasive carcinoma [2].

References